---
title: "Persistent Interferon-Linked Whole-Blood Signatures in COVID-19 Convalescence"
id: "pubmed-42673338"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42673338"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42673338/"
doi: "10.1002/jmv.71133"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Persistent Interferon-Linked Whole-Blood Signatures in COVID-19 Convalescence
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42673338
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42673338/)
- **DOI:** [10.1002/jmv.71133](https://doi.org/10.1002%2Fjmv.71133)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Study used longitudinal within-person comparisons with pre-infection baselines to identify blood transcriptomic changes after SARS-CoV-2 infection, minimizing inter-individual variability and time-related drift. - Adults sampled at baseline (T0), ~3 months (T1), and ~6 months (T2) post-infection; matched COVID-19‑naïve controls sampled across the same timepoints. - COVID-19‑naïve status in controls was confirmed using a multiplex anti-nucleocapsid IgG assay covering multiple variant antigens. - Whole-blood RNA-seq (PAXgene) data were analyzed with **DESeq2** incorporating time point and participant; genes changing over time in controls were excluded to prioritize infection-linked signals. - After excluding control-associated genes, there were marked transcriptional changes during convalescence: 782 genes (T1 vs T0) and 655 genes (T2 vs T0) with p < 0.05. - Pathway analysis used pre-ranked GSEA with MSigDB; pathway clusters were organized with aPEAR. - **Interferon-α** and **interferon-γ** signatures were enriched at both ~3 and ~6 months post-infection, with a core set of interferon-associated genes remaining elevated across convalescence. - Findings indicate durable whole-blood immune-defense programs and sustained interferon signaling detectable up to 6 months after infection. - Authors propose that prolonged post-infectious immune activation may contribute to extended **thromboinflammatory** risk observed after COVID-19. - Keywords reported: COVID‑19; Interferons; RNA‑Seq; Transcriptome.
## Clinical Analysis & Structured Key Points
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Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA."), [Florencia Schlamp](https://pubmed.ncbi.nlm.nih.gov/?term=Schlamp+F&cauthor_id=42673338)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-1 "Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA."), [Michael Tuen](https://pubmed.ncbi.nlm.nih.gov/?term=Tuen+M&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Ralf Duerr](https://pubmed.ncbi.nlm.nih.gov/?term=Duerr+R&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Marie Samanovic-Golden](https://pubmed.ncbi.nlm.nih.gov/?term=Samanovic-Golden+M&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Mark J Mulligan](https://pubmed.ncbi.nlm.nih.gov/?term=Mulligan+MJ&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Tessa J Barrett](https://pubmed.ncbi.nlm.nih.gov/?term=Barrett+TJ&cauthor_id=42673338)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#full-view-affiliation-1 "Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA.") Affiliations Expand ### Affiliations * 1 Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA. * 2 NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. * PMID: **42673338** * DOI: [ 10.1002/jmv.71133 ](https://doi.org/10.1002/jmv.71133) Item in Clipboard # Durable Interferon-Linked Blood Signatures During COVID-19 Convalescence Alexander Ferrena et al. J Med Virol. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID J Med Virol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Med+Virol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Med+Virol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42673338/) . 2026 Sep;98(9):e71133. doi: 10.1002/jmv.71133. ### Authors [Alexander Ferrena](https://pubmed.ncbi.nlm.nih.gov/?term=Ferrena+A&cauthor_id=42673338)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-1 "Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA."), [Florencia Schlamp](https://pubmed.ncbi.nlm.nih.gov/?term=Schlamp+F&cauthor_id=42673338)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-1 "Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA."), [Michael Tuen](https://pubmed.ncbi.nlm.nih.gov/?term=Tuen+M&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Ralf Duerr](https://pubmed.ncbi.nlm.nih.gov/?term=Duerr+R&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Marie Samanovic-Golden](https://pubmed.ncbi.nlm.nih.gov/?term=Samanovic-Golden+M&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Mark J Mulligan](https://pubmed.ncbi.nlm.nih.gov/?term=Mulligan+MJ&cauthor_id=42673338)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-2 "NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA."), [Tessa J Barrett](https://pubmed.ncbi.nlm.nih.gov/?term=Barrett+TJ&cauthor_id=42673338)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42673338/#short-view-affiliation-1 "Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA.") ### Affiliations * 1 Leon H. Charney Division of Cardiology, Department of Medicine, Cardiovascular Research Center, NYU Grossman School of Medicine, New York, New York, USA. * 2 NYU Langone Vaccine Center, and Division of Infectious Diseases and Immunology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. * PMID: **42673338** * DOI: [ 10.1002/jmv.71133 ](https://doi.org/10.1002/jmv.71133) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Thrombotic risk in COVID-19 extends beyond acute illness, including in nonhospitalized individuals, suggesting that thrombo-inflammatory biology may persist during recovery. Longitudinal sampling with pre-infection baselines is needed to distinguish infection-associated signals from inter-individual variability and time-related drift in blood gene expression. To define coordinated, time-resolved whole-blood transcriptomic programs during SARS-CoV-2 convalescence using longitudinal within-person comparisons before and after infection, alongside COVID-19-naïve controls. Adults were sampled longitudinally with specimens collected before SARS-CoV-2 infection (T0) and at ~3 months (T1) and ~6 months (T2) post-infection; COVID-19-naïve controls were sampled across matched timepoints. COVID-19-naïve status was confirmed using a multiplex anti-nucleocapsid IgG assay spanning multiple variant antigens. Whole-blood RNA-seq (PAXgene) was analyzed with DESeq. 2 using models that incorporated time point and participant. To prioritize infection-linked changes, genes differentially expressed over time in controls were identified and excluded from comparisons between COVID-19 time points. Pathways were assessed by pre-ranked GSEA (MSigDB) and clustered with aPEAR. After excluding control-associated genes, COVID-19 convalescence remained associated with marked transcriptional remodeling (T1 vs. T0: 782 genes; T2 vs. T0: 655 genes; p < 0.05) and persistent pathway-level changes. Interferon-α and interferon-γ signatures were enriched at both T1 and T2, and a core set of interferon-associated genes remained elevated across convalescence. SARS-CoV-2 infection is followed by durable whole-blood immune-defense programs, including persistent interferon signaling, detectable up to 6 months post-infection. These sustained signatures support a model of prolonged post-infectious immune activation that may contribute to extended thromboinflammatory risk. **Keywords:** COVID‐19; Interferons; RNA‐Seq; Transcriptome. © 2026 Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## References 1. 1. L. Ortega‐Paz, D. Capodanno, G. Montalescot, and D. J. Angiolillo, “Coronavirus Disease 2019–Associated Thrombosis and Coagulopathy: Review of the Pathophysiological Characteristics and Implications for Antithrombotic Management,” Journal of the American Heart Association 10 (2021): e019650. 2. 1. E. M. Conway, N. Mackman, R. Q. Warren, et al., “Understanding COVID‐19‐Associated Coagulopathy,” Nature Reviews Immunology 22 (2022): 639–649. 3. 1. C. Q. Pratt, A. F. Dalton, E. H. Koumans, et al., “Thrombotic Events and Stroke in the Year After COVID‐19 or Other Acute Respiratory Infection,” Emerging Infectious Diseases 31 (2025): 3–10. 4. 1. B. K. Manne, F. Denorme, E. A. Middleton, et al., “Platelet Gene Expression and Function in Patients With COVID‐19,” Blood 136 (2020): 1317–1329. 5. 1. Y. Zaid, F. Puhm, I. Allaeys, et al., “Platelets Can Associate With SARS‐CoV‐2 RNA and Are Hyperactivated in COVID‐19,” Circulation Research 127 (2020): 1404–1418. 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